부산대학교 도서관

BACKGROUND AND PURPOSE:: Pharmacological inhibition of beta-amyloid (Aβ) induced reactive gliosis may represent a novel rationale to develop drugs able to blunt neuronal damage and slow the course of Alzheimerʼs disease (AD). Cannabidiol (CBD), the main non-psychotropic natural cannabinoid, exerts in vitro a combination of neuroprotective effects in different models of Aβ neurotoxicity. The present study, performed in a mouse model of AD-related neuroinflammation, was aimed at confirming in vivo the previously reported antiinflammatory properties of CBD. EXPERIMENTAL APPROACH:: Mice were inoculated with human Aβ (1–42) peptide into the right dorsal hippocampus, and treated daily with vehicle or CBD (2.5 or 10 mg kg, i.p.) for 7 days. mRNA for glial fibrillary acidic protein (GFAP) was assessed by in situ hybridization. Protein expression of GFAP, inducible nitric oxide synthase (iNOS) and IL-1β was determined by immunofluorescence analysis. In addition, ELISA assay of IL-1β level and the measurement of NO were performed in dissected and homogenized ipsilateral hippocampi, derived from vehicle and Aβ inoculated mice, in the absence or presence of CBD. KEY RESULTS:: In contrast to vehicle, CBD dose-dependently and significantly inhibited GFAP mRNA and protein expression in Aβ injected animals. Moreover, under the same experimental conditions, CBD impaired iNOS and IL-1β protein expression, and the related NO and IL-1β release. CONCLUSION AND IMPLICATIONS:: The results of the present study confirm in vivo anti-inflammatory actions of CBD, emphasizing the importance of this compound as a novel promising pharmacological tool capable of attenuating Aβ evoked neuroinflammatory responses.British Journal of Pharmacology (2007) 151, 1272–1279; doi:10.1038/sj.bjp.0707337